This application is for the replacement of a heavily utilized but obsolete and unreliable twelve year old quadrupole gas chromatograph-mass spectrometer (GC-MS) with a state of the art GC-MS for high sensitivity quantitation, in particular the use of negative ion-chemical ionization (NI-CI) selected ion monitoring (S.I.M) methods. The instrument would become a part of a shared mass spectrometry laboratory, in operation for over twelve years, which serves a user group of local investigators as a University research resource, as well as a national user group of clinical investigators as an N.I.H. supported Mass Spectrometry Clinical Research Resource. The intramural major user group is an interdisciplinary team of investigators primarily located in the Department of Pharmacology at the Medical University of South Carolina supported by a variety of N.I.H. and other research grants and united under an N.I.H. Program Project Grant. The national user group consists of investigators from any of the 75 N.I.H. supported General Clinical Research Centers (GCRC's) located in major medical centers throughout the country who are supported by their GCRC grants, the MS Resource grant, and other N.I.H. research grants. The requested instrument would be used for high sensitivity NI-CI GC-MS S.I.M. analysis of eicosanoids, beta-receptor blocker and other drugs, vitamin D metabolites, steroids, small peptides, and other endogenous compounds and for research in sample preparation methodology for such analyses. The sample preparation methodology research is focussed upon the use of immunoaffinity extraction and automated gas phase derivatization. The requested instrument would also be used for GC-MS isotope ratio measurements of amino acids, keto-acids, glucose, choline, ascorbic acid, Beta-carotene, vitamin A, and other endogenous compounds in relation to clinical studies using stable isotope tracers. Other applications would include GC-MS S.I.M. quantitation in E.I. and positive ion C.I. mode of drugs and a variety of endogenous compounds for present and future clinical studies by GCRC investigators. As part of a shared mass spectrometry laboratory with over twelve years experience serving a diverse user group on a local and national scale, and with ongoing collaboration with presently eighteen investigator groups at eight different institutions, the requested instrument would be assured of maximal utilization.